I've been tinkering with the idea of using single supply laptop SMPS in audio, but I am starting to question whether the negative rail in an isolated SMPS can be treated as ground, as in it would be 2 quadrant and can be used to return load currents.

I've seen these supplies tied in series to make dual supplies, and it seems to me this works because current are individually sourced/sunk by the upper/lower supplies. Is this true?

I canīt understand well the question, but as I believe, you want to use two smpsīs to generate a split power supply. Effectively, you can, but there is a little trouble: ussualy there is a .0047uF 1KV or so linking negative output to -VDC bus, without the smps can oscillate. And the line filter also has two Y caps of about .0047uF 1KV between each line wire and negative output, if the supply has no the ground terminal. So, this capīs can put little amounts of 100/120Hz in the rails, so if the amplifier has big amounts of gain, it can hum a little.

Sorry about the confusion, I mean to play with some of the more antique single supply circuits, cap or transformer coupled outputs with one end of the load tied to "ground", or in this case, the negative supply from a single SMPS.

If I understand this correctly, the speaker load return ground would need to both source and sink current, and thus a negative linear regulator wouldn't do that job very well because it could only sink current.

I was just wondering if the negative rail on a SMPS would do a better job at this.

Why to use a regulator!!!. None amplifier needs a regulator, nor positive nor negative rails. If you want add it, you can, but the amp doesnīt need such a regulator. And, the negative rail only sinks currents in any circuit. The Ac path only is established between output power stage, load and capacitive coupling. The current in the positive and negative rails flows always in the same direction.

I do understand this is a compromise, and the fact that I have limited understanding in the inner workings of a SMPS makes me concerned whether the single supply circuits from the old days would adapt well to new technology.

I was under the impression that a single linear supply returning currents to the main filter cap / transformer secondary can be effective, but I am not so sure about a SMPS.

Looking into a PS from its output terminals, all them are equal in respect to the current flow: a linear. a SMPS, a battery and unregulated. The differences between them are the output internal resistance and eventually the ripple or noise from it.